Low circulating levels of bisphenol-A induce cognitive deficits and loss of asymmetric spine synapses in dorsolateral prefrontal cortex and hippocampus of adult male monkeys

J Comp Neurol. 2015 Jun 1;523(8):1248-57. doi: 10.1002/cne.23735. Epub 2015 Feb 17.

Abstract

Bisphenol-A (BPA) is widely used in the manufacture of plastics, epoxy resins, and certain paper products. A majority of the population in the developed world is routinely exposed to BPA from multiple sources and has significant circulating levels of BPA. Although BPA is categorized as an endocrine disruptor with a growing literature on adverse effects, it is uncertain whether cognitive dysfunction is induced in humans by exposure to BPA. The present study examined the impact of BPA in primate brain by exposing adult male vervet monkeys for 4 weeks continuously to circulating levels of BPA that were in the range measured in studies of humans environmentally exposed to BPA. This regimen of exposure to BPA decreased both working memory accuracy and the number of excitatory synaptic inputs on dendritic spines of pyramidal neurons in two brain regions that are necessary for working memory (prefrontal cortex and hippocampus). These observed behavioral and synaptic effects were ameliorated following withdrawal from BPA. As Old World monkeys (e.g., vervets) and humans share some uniquely primate morphological, endocrine, and cognitive traits, this study indicates the potential for significant cognitive disruption following exposure of humans to BPA.

Keywords: dopamine; endocrine disruptor; working memory.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Air Pollutants, Occupational / blood
  • Air Pollutants, Occupational / toxicity*
  • Animals
  • Benzhydryl Compounds / blood
  • Benzhydryl Compounds / toxicity*
  • CA1 Region, Hippocampal / drug effects*
  • CA1 Region, Hippocampal / ultrastructure
  • Chlorocebus aethiops
  • Cognition Disorders / chemically induced*
  • Cognition Disorders / pathology
  • Dendritic Spines / drug effects
  • Dendritic Spines / ultrastructure
  • Environmental Exposure
  • Male
  • Memory, Short-Term / drug effects
  • Microscopy, Electron
  • Models, Animal
  • Neuropsychological Tests
  • Phenols / blood
  • Phenols / toxicity*
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / ultrastructure
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / ultrastructure
  • Synapses / drug effects*
  • Synapses / ultrastructure

Substances

  • Air Pollutants, Occupational
  • Benzhydryl Compounds
  • Phenols
  • bisphenol A